The objectives of this program are to investigate the biomechanical behavior of red blood cells, white blood cells, endothelial cells, smooth muscle cells and other components of the vasculature; to study the micromechanics and molecular basis of cell-cell interactions; and to assess the roles of these cell properties in microcirculatory regulation in health and disease. The rheological properties of normal and abnormal blood cells, endothelial cells and smooth muscle cells will be studied by micromechanical techniques. The experimental results will be subjected to computational analysis and serve as the basis of theoretical modeling. These findings will be correlated with the molecular organization of the cell membrane, especially the membrane proteins. The Program will employ a multidisciplinary, systematic approach involving parallel experimental and theoretical investigations, which cover the spectrum ranging from molecular biology tot he microcirculation. Experiments will be conducted to study the effects of experimental manipulations of the molecular characteristics of the cell membrane on (a) the biomechanical properties of the cells and (b) the micromechanical and molecular energetics of their interactions (neutrophil-neutrophil, leukocyte-endothelial, erythrocyte-macrophage, etc.) The effects of alterations of blood cell properties on flow dynamics will be studied in the microcirculation; particular emphasis will be placed on WBC kinetics and the attendant changes in circulatory functions. The coordinated effort is aimed at elucidating the molecular basis and physiological roles of the biomechanical behavior of red blood cells, white blood cells, endothelial cells and vascular smooth muscle cells, with the ultimate goal of providing the fundamental knowledge needed to improve diagnosis and treatment of cardiovascular and blood diseases.